E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Antiretroviral-Naive, HIV-1 Infected Adults |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008922 |
E.1.2 | Term | Chronic infection with HIV |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate a superior renal safety profile in subjects receiving ABC/3TC FDC compared to TDF/FDC FDC, both administered with efavirenz |
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E.2.2 | Secondary objectives of the trial |
• To compare changes in markers of renal function in subjects receiving ABC/3TC FDC compared to TDF/FTC FDC, both administered with efavirenz • To compare changes in bone mineral density in subjects defined as above • To compare safety and tolerability in subjects defined as above • To compare fasting lipid profiles in subjects defined as above • To compare virologic response in subjects defined as above • To compare immunologic response in subjects defined as above • To evaluate viral resistance patterns in subjects experiencing virologic failure • To compare healthcare resource utilization in subjects receiving ABC/3TC FDC compared to TDF/FTC FDC, both administered with efavirenz
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject is >or equal to 18 years of age. 2. Subject is antiretroviral-naïve (defined as having no previous therapy with any NNRTI and < or equal to 14 days of prior therapy with any other antiretroviral). 3. Subject has plasma HIV-1 RNA >or equal to1,000 copies/mL at screening. This test may be repeated once within the 45-day screening window. 4. Subject is willing and able to understand and provide written informed consent prior to participation in this study. 5. A female is eligible to enter and participate in the study if she is of: a. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or, b. Child-bearing potential, has a negative pregnancy test at screen and agrees to one of the following methods of contraception (any contraception method must be used consistently and correctly, i.e., in accordance with both the approved product label and the instructions of a physician): • Complete abstinence from intercourse from 2 weeks prior to administration of the investigational products, throughout the study, and for at least 2 weeks after discontinuation of all study medications • Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide). Hormonal contraception will not be considered adequate for inclusion into this study • Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year. • Sterilization (female subject or male partner of female subject). All subjects participating in the study should be counselled on the practice of safer sex. 6. Prior to randomization, subjects must have been screened and be negative for the HLA-B*5701 allele. Test may be performed by local laboratory and results must be available for source document verification according to local practices.
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E.4 | Principal exclusion criteria |
1. Subject is in the initial acute phase of a CDC Clinical Category C infection at Baseline. Subjects may be enrolled provided they are receiving treatment for such infections and are clinically improving at the Baseline visit. 2. Subject is enrolled in one or more investigational drug protocols, which may impact HIV RNA suppression. 3. Subject is, in the opinion of the Investigator, unable to complete the study dosing period and protocol evaluations and assessments. 4. Subject is either pregnant or breastfeeding. 5. Subject suffers from a serious medical condition, which in the opinion of the Investigator would compromise the safety of the subject. 6. Subject has a pre-existing mental, physical, or substance abuse disorder which, in the opinion of the Investigator, may interfere with the subject’s ability to comply with the dosing schedule and protocol evaluations and assessments. 7. Subject has a history of inflammatory bowel disease or intestinal malignancy, intestinal ischemia, malabsorption, or other gastrointestinal dysfunction, which, in the opinion of Investigator, may interfere with drug absorption or render the subject unable to take oral medication. 8. Subject has any acute laboratory abnormality at screening, which, in the opinion of the Investigator, would preclude the subject’s participation in the study. If subjects are found to have an acute Grade 4 laboratory abnormality at screening, this test may be repeated once within the 45-day screening window. Any verified Grade 4 laboratory abnormality would exclude a subject from study participation. 9. Subject has an estimated creatinine clearance within the screening period <50mL/min via the Cockcroft-Gault method as determined and calculated by the central laboratory. Re-testing will not be permitted. 10. Alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN). 11. Subjects with a history of thyroid disease, hyperparathyroid disease, chronic hyper or hypocalcemia, vitamin D deficiency, or receiving thyroid hormone or parathyroid hormone replacement within 28 days prior to screening are excluded. 12. Subjects with a history of rheumatoid arthritis or other systemic inflammatory arthritis are excluded. 13. Subjects who are hepatitis B virus surface antigen (HBVsAg) positive at screening are excluded. 14. Subject requires treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days prior to screening, or has an anticipated need for these agents within the study period. 15. Subject has received treatment with an HIV-1 immunotherapeutic vaccine or any agents with documented activity against HIV-1 in vitro within 28 days prior to Screening, or an anticipated need during the study. 16. Subjects who require treatment with any of a protocol specified list of medications within 28 days of commencement of investigational product, or an anticipated need during the study. 17. Subject has a history of allergy to any of the protocol-specified medications or any excipients therein. 18. Subject has evidence of genotypic resistance at screening (according to central lab interpretation) or prior documented evidence of genotypic and/or phenotypic (above threshold for reduced susceptibility) resistance to any of the following drugs: efavirenz, abacavir, lamivudine, tenofovir, emtricitabine. 19. Subjects who are unsuitable for DEXA scanning should be excluded, including 1) Less than three vertebra in the range of L1 to L4 that are suitable for BMD measurement by DEXA, or 2) Bilateral hip replacement.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Change from baseline in estimated GFR, calculated by MDRD equation, at week 48. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |